Previous work from this laboratory has shown that about one third of patients with advanced heart failure (HF) have deficiencies in functioning of natural killer (NK) lymphocytes, cells important in immunity to tumors and viruses. Almost half of such patients no longer can mount a delayed hypersensitivity responses to intradermal challenge with recall antigens. Indeed, such skin test anergy is a marker for mortality in patients with coronary artery disease. Twelve percent of the patients show elevated white blood cell counts, indicative of infection. The interrelationships of these parameters and mechanisms of this immunologic dysfunction will be examined in this proposal. There are factors intrinsic to HF which predispose patients to immunologic dysfunction. Elevated plasma norepinephrine (NE) is associated with advanced HF, is related to increased mortality and sudden death risk and has been shown to be associated with reduced immune responses. The theory to be tested is that the high NE environment of HF is a major factor in triggering a reduction in NK cytotoxicity (ability to augment cytotoxicity in response to cytokine stimulants) and delayed type hypersensitivity (as indicated in the skin test to recall antigens) and that the resulting dysfunction occurs in the cytokine system. One clinical manifestation of this is an increased susceptibility to infection, as measured here by increased white blood cell counts. The design for this study will compare anergic versus nonanergic HF patients, all New York Heart Association class III or IV. Age and gender-matched normal controls will be included for all immunological tests. Patients will be tested when the HF is maximal and then at 3 months after medical optimization therapy to determine whether anergy is reduced as cardiovascular function improves. As evidence accumulates that there is immune dysfunction in HF related to the etiology, course and treatment of the disease, a new role for nursing care of these patients is emerging. Immunologic testing can provide a powerful tool to identify patients at risk for complications so that they can be targeted for special monitoring, education and intervention.